This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In order to prevent the ongoing spread of HIV and other STDs, it is imperative that an effective topical microbicide product be developed and made available for use. This project proposes to develop a combination topical microbicide product, targeted primarily at preventing the transmission of HIV, and also have activity in preventing other STDs. The product will be made up of novel compounds (a peptide and a fusion inhibitor) which exert synergistic effects on one another, thereby attacking pathogens from as many angles as possible, while preserving the integrity and microflora populations of the rectal and vaginal environments. Product formulation is guided by iterative safety, toxicity and efficacy assays (in vitro, ex vivo and in vivo). Our macaque model is used to determine the most feasible and effective delivery mechanisms, compound availability and product safety. These experiments in the macaque model are essential in filling the gap between laboratory and clinical studies.